Methyltransferase-inhibition interferes with neuronal differentiation of P19 embryonal carcinoma cells.
We have analyzed the importance of substrate methylation by S-adenosylmethionine-dependent methyltransferases for neuronal differentiation of P19 embryonal carcinoma cells. We show that treatment of cells with methyltransferase inhibitor adenosine dialdehyde (AdOx) interferes with neuronal differentiation. Retinoic acid (RA) and AdOx co-treated cells had a decreased number of neurites and a flattened morphology compared with cells differentiated by RA. Also, the amount of neuronal class III tubulin (Tuj1) decreased from 76% to 9.6% with AdOx-treatment. Gene expression levels of wnt-1, brn-2, neuroD, and mash-1 were also down-regulated by AdOx-treatment. But AdOx-treatment did not up-regulate BMP-4 and GFAP genes. Treatment of RA decreased E-cadherin expression during neuronal differentiation. However, in AdOx/RA co-treated cells, E-cadherin expression was restored to the control level. Also, mRNA expression of N-cadherin decreased with AdOx-treatment. Taken together, these data show that methylation reactions might influence the cell-fate decision and neuronal differentiation of P19 cells.
Hong
Sukchul
S
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Heo
Jieun
J
Lee
Sangjin
S
Heo
Seok
S
Kim
Sung-Soo
SS
Lee
Young-don
YD
Kwon
Moosik
M
Hong
Sungyoul
S
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D018236:Carcinoma, Embryonal; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology / Q000201:enzymology; D008745:Methylation / Q000187:drug effects; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000201:enzymology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects
D015820:Cadherins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C027579:periodate-oxidized adenosine; D008780:Methyltransferases; D000241:Adenosine